Promoting Smoke-Free Homes Through Biomarker Feedback Documenting Child Exposure to Tobacco Toxins: Protocol for a Randomized Clinical Trial

Background Exposure to secondhand smoke (SHS) early in life increases the risk of sudden infant death syndrome (SIDS), asthma, and respiratory illnesses. Since children’s primary exposure to SHS occurs in the home, these most vulnerable members of our society are not fully protected by recent increases in the adoption of smoking bans in public spaces. Although exposure to SHS is a quickly reversible cause of excess morbidity, few low-income homes strictly enforce smoking restrictions. Objective This study aims to test a novel approach to motivate the adoption of home smoking restrictions and to eliminate child SHS exposure by providing parents with objective data documenting home SHS exposure and “biomarker feedback” of child ingestion of tobacco toxins, that is, objective, laboratory-based results of assays performed on child urine, documenting levels of nicotine; cotinine; and NNAL (4-[methylnitrosamino]-1-[3-pyridyl]-1-butanol), which is a metabolite of the known tobacco carcinogen NNK (4-[methylnitro-samino]-1-[3-pyridyl]-1-butanone). Methods From 2011 to 2013, 195 low-income, female smokers with children aged ≤10 years residing in their homes were recruited into a two-arm randomized clinical trial. Participants were assigned to one of two groups: biomarker feedback (n=98) and health education (n=97). In-home assessments were administered at baseline, week 16, and week 26. Children’s home SHS exposure and nicotine, cotinine, and NNAL levels from urine samples, measured through a passive nicotine dosimeter and a surface sample of residual tobacco smoke (ie, thirdhand smoke), were collected at all three time points. Primary outcome was dosimeter-verified, self-reported complete home smoking restrictions at 6 months after randomization. Secondary outcomes included parental self-report of smoking behavior change and child urine tobacco toxin (biomarker) change. Results Data collection and analyses are complete, and the results are being interpreted. Conclusions The study protocol describes the development of a novel community-based controlled trial designed to examine the efficacy of biomarker feedback documenting home and child exposure to SHS on parental smoking behavior change. International Registered Report Identifier (IRRID) RR1-10.2196/12654

1 P60 MD003422-01 7 ZMD1 PA (13) AHLUWALIA, J community engagement among minority and underserved populations around initiatives to eliminate health disparities. He will assist the Director in all activities and will Chair the Executive Committee meetings in the Director's absence. His primary role will be as the point person for all non-University activities.
Eileen M. Harwood, Ph.D. -Assistant Professor in the School of Public Health, Division of Epidemiology and Community Health (1.20 calendar months), will serve as Evaluation Director within the Administrative Core and of the CeHDRET.

Environment:
The institutional commitment to the pursuit of minority health and health disparities research, including provision of resources, administrative authority and recognition is excellent. To maximize the likelihood of the endeavor's success, the UMN Medical School will commit substantial new resources to support this initiative. This commitment will include: 1) a start-up fund of $1 million; 2) a recurring fund of $300,000 a year; 3) 8,000 sq ft of contiguous University office space, and 1,500 sq ft of new space in the North side community for community-based research and programs and 4) the University is making a commitment of $100,000, increased each year by the same amount, to a total recurring amount of $400,000 a year (beginning in year 4). The scientific environment(s) in which the work will be done will contribute to the probability of success. The proposed studies will benefit from unique features of the scientific environment(s), and easy access to subject populations institutional support is evidence.

Budget Recommendations: Appropriate
Administrative Comments: one main concern is the time commitment of the PI

CRITIQUE 4 OF THE OVERALL CENTER
Significance: The research goals of the Center address two important problems which affect African American health: chronic kidney disease and tobacco use. The two projects differ substantially in not only their area of focus (smoking cessation vs. chronic kidney disease) but, perhaps more importantly, in their approach. In fact, it is difficult to discern any unifying theme between the two projects except African American health most generally. Without any unifying or common shared approaches or themes, it is unclear what opportunities for synergy and collaboration will develop.
Approach: Again, because the aims, areas, and approaches in the two projects differ so widely, the potential for synergism between the two main projects is limited. Synergism between the community outreach project on smoking cessation and Project 1, a community-based biofeedback intervention to reduce ETS exposure among children, may be possible. The second project, with its focus on data analysis from a national database of medicare claims, seems isolated from the rest of the Center's activities. There is little to no opportunity, for example, for involvement/contributions from or to the community outreach core or the research and education core and project 2. It is unclear why it is proposed as a project in this application, rather than a separate research project. On the positive side, the Center's commitment to encouraging and fostering new investigators, even in the absence of NIH-1 P60 MD003422-01 8 ZMD1 PA (13) AHLUWALIA, J funded pilot grant program, is impressive and shows the extent of institutional commitment to the Center.

Innovation:
The specific project ideas are not particularly unique or innovative. The most innovative part of the application may be the community outreach core, whose activities (though not research per se) involve community organizations in a substantial way to address subjects of expressed concern and relevance to community members.

Investigators:
The investigators are almost all extremely well-qualified and experienced in minority and disparities research.
Environment: Institutional support is impressive: two pilot grant programs and recruitment of 5 new faculty; total of almost $3 million over 5 years from both Medical school and university is pledged. University of Minnesota has invested substantial resources in the Center for Health Disparities that is already established and productive.
Minnesota has a relatively low percent of minorities (11.8%, as compared to 26% nationally). Although this would argue against the establishment of a NCMHD Center of Excellence in Minneapolis, it seems likely that the coasts are over-represented and having a mid-western presence may be advantageous. Also, the minority population of Minnesota is growing. The Administrative Core will serve as the primary organizing structure for the University of Minnesota Center for Health Disparities Research, Engagement, and Training (CeHDRET). Upon receipt of the Center of Excellence P60 award, the planned activities will be seamlessly integrated with the Medical School's Program in Health Disparities. The Administrative Core will: 1) Coordinate the Research Training, Community Engagement, and Research Cores, and at a high level, 1 P60 MD003422-01 10 ZMD1 PA (13) AHLUWALIA, J Environment: There is excellent institutional and community support for the proposed activities. The detail with which duties are outlined ensures that the Center will have good focus to meet its goals.

Budget recommendations:
The budget is commensurate with personnel requirements and proposed activities.

CRITIQUE 2 OF THE ADMINISTRATIVE CORE
Approach: The Administrative Core will serve as the primary organizing structure for the University of Minnesota for Health Disparities Research, Engagement, and Training (CeHDRET). The arrangements and organizational structure are adequately developed, well reasoned and appropriate to the aims of the center. The application, also describes how day-to-day management will be accomplished. The Administrative Core will: 1) Coordinate the Research Training, Community Engagement, and Research Cores, and at a high level, the two Research Projects; 2) Manage operations; 3) Coordinate disparities activities across the University; 4) Promote the Center's Activities; 5) Organize and staff annual treats of Center leadership and members; 6) Recruit and retain minority faculty and faculty conducting health disparities and minority health research; 7) Facilitate communication; and, 8) Conduct evaluation activities of the Center.

Approach:
The Principal Investigator (and Administrative Core Director) and Executive Director, Dr. Ahluwalia, reports to Deborah Powell, the Medical School Dean. The Director will have substantial authority, responsibility, and resources and will lead the allocation of the University and community space, as well as the NIH P60 and institutional funds. The leadership team will also include Kola Okuyemi, MD (Deputy Director and Director of the Community Engagement Core), Selwyn Vickers, MD (Director of the Research Training Core and past PI of the UAB EXPORT), Susan Everson-Rose, PhD (Director of the Research Core), Mary Story, PhD (Co-Director of the Research Core), and Kathleen Call, PhD (Co-Director of the Community Engagement Core. The Center will have three Boards. An External Advisory Board comprised of seven members of national prominence who have research expertise, gender, and ethnic diversity. The Internal Advisory Board will be comprised of eight institutional leaders; six Deans, the Vice President for Equity and Diversity, and the Director of our Comprehensive Cancer Center. Finally, the Community Collaborative Board will include 10members from various sectors of the Twin Cities, and one member each from our two lead Community Partners. The Administrative Core builds upon active community/academic partnerships with a demonstrated commitment to provide health outreach to vulnerable populations and research, training and educational opportunities to populations most affected by health disparities. The Administrative Core is very well described and has excellent structure. The long-term Management is not very well articulated.

Investigators:
The qualifications, experience, and administrative competence of the Administrative Core Director are appropriate. The individuals providing key management and decision-making comprise a uniquely synergistic blend of critical skills and disciplinary expertise to develop and implement innovative approaches to prevailing problems embedded in health disparities. Jasjit S. Ahluwalia, M.D., M.P.H., M.S. -Associate Dean and Professor of Medicine and Professor of Epidemiology and Community Health, will serve as Director of the Administrative Core and the CeHDRET and Principal Investigator of the award.

Environment:
The institutional commitment is evident to support minority health and health disparities research and other proposed activities, including provision of resources, and administrative authority. There is a firm institutional commitment for space to accommodate the dedicated office personnel.

Approach:
The Administrative Core is directed by the CeHDRET PI -Dr. Ahluwalia. The Center Co-Director -Dr. Kolawole Okuyemi will serve as Deputy Director and Dr. Eileen Harwood (Assistant Professor of in the School of Public Health) will serve as the Evaluation Director. An Administrative Director at 0.50 FTE is yet to be named. Other key personnel in this core include a Web Master and a Program Manager. Eight specific aims (functions) are defined for the core. The core will be located in the Medical School although note is made that it will be a highly visible institution-wide resource. Governance is well delineated with the Director reporting to the Medical School Dean. An Executive Committee comprising the PI and core directors will responsible for the Center's operation. Provision is made for an External Advisory Committee of seven members from different institutions. Eight institutional leaders including the Deans of the Medical, Nursing, Dentistry, Public Health and Pharmacy will provide advice to the Center on issues of strategic planning. A 10-member Community Collaborative Board is also proposed. The composition of the various committees and their functions are well conceived and adequately defined. An excessive number of meetings is proposed for the Community Collaborative Board (6 times/year). A comprehensive evaluation plan is presented based on the Logic Model.

Investigator:
The investigators are well qualified.

Environment:
The environment is well resourced and more than adequate.

Budget Recommendations: The budget is appropriate
Administrative Comments: None

CRITIQUE 4 OF THE ADMINISTRATIVE CORE
Approach: Executive committee (PIs and core directors) will meet bi-weekly. External advisory board will meet annually. Internal advisory board will meet annually: primarily deans of the school of public health, pharmacy, nursing, dentistry, and medical schools. Community Collaborative Board will meet every 2 months.
Investigator: Directors Dr. Ahluwalia with Dr Harwood (evaluation director) and Dr. Okuyemi (Deputy director). Dr. Ahluwalia will devote 25% effort to the administrative core, which is appropriate. Paul, Minnesota, in efforts to improve minority health and reduce health disparities. The Community Engagement & Outreach Core has two specific aims: Aim 1: To establish a communityacademic partnership that will provide a unifying and transformative organizational framework for improving minority health in the Twin Cities of Minnesota; Aim 2: To engage community partners from the local African American and African immigrant (Somali) communities in the dissemination of interventions to promote fruit and vegetable consumption and reduce tobacco use. Core activities, guided by the principles of communitybased participatory research (CBPR), will be a collaborative effort among the University of Minnesota, the 1 P60 MD003422-01 12 ZMD1 PA (13) AHLUWALIA, J Stairstep Foundation (which has a coalition of 32 African American churches in the Twin Cities), and the Minnesota International Health Volunteers (MIHV). For Aim 1, we will focus on the five key phases that define CBPR: partnership building, capacity building, needs assessment, community action plan (CAP) development, and CAP implementation and evaluation. For Aim 2, we propose two activities. First, we will partner with the Stairstep Foundation to disseminate Body & Soul, an evidence-based program to promote fruits and vegetables consumption in African Americans. Second, we will partner with MIHV to develop a culturally-targeted community-based intervention to reduce tobacco use in the Somali community. We also will work closely with the CeHDRET Research Training and Education Core to engage trainees in community research and outreach activities. Through partnership and capacity building, we plan to work collaboratively to create mutually beneficial and sustainable programs with the goal of producing knowledge that may be directly applied to improving community health. Along with our community partners, we plan to develop, implement, and evaluate innovative community engagement and outreach programs with the ultimate goal of reducing health disparities.

Significance:
The objective is to engage minority communities in health promotion programs to reduce their disproportionate cancer and cardiovascular risk and reduce cancer and cardiovascular risk factors. The long-term goal of the Center for Health Disparities Research, Engagement, and Training (CeHDRET) is to create an informed, empowered, and activated community and research/practitioner base to collaborate on improving minority health. The Center aims to bridge University scientists and partner institutions and community members by removing barriers and incentivizing collaboration opportunities. This builds upon other programs in place at the University, which serve as models of success, e.g., the Urban Outreach/Engagement Center, Program in Health Disparities Research Community Collaborative Pilot Grants where university scientists and community partner are Co-Investigators.
Approach: Establish community-academic partnership to provide unifying and transformative organizational framework for improving minority health in the Twin Cities, engage community partners from local African American and African immigrant communities to disseminate interventions to promote fruit and vegetable consumption and reduce tobacco use. Guided by CBPR (community-based participatory research) principles, the collaborative effort among the University of Minnesota, the Stairstep Foundation (coalition of 32 African American churches) and the Minnesota International Health Volunteers is to develop, implement, and evaluative innovative community engagement and outreach with the goal of reducing health disparities. Partnering with SF, this Core will disseminate Body & Soul, an evidence-based program to promote fruit and vegetable consumption, and partner with MIHV to develop a targeted intervention to reduce tobacco use. This Core will work closely with the Research Training and Education Core to engage trainees in community research and outreach.
A 9-member Steering Committee will convene with 3 members from each SF, MIHV, and UM. They will develop a community action plan that drives the focus of research efforts based on community needs. There is a Community Collaborative Board in place (letters of support included), which will provide ongoing guidance to the steering committee, and there will be Community Dialogue Sessions (monthly) and Distinguished Scholar Series meetings (quarterly). A community partner assessment will evaluate the community's experience with the partnership.
Investigator: Core Director is presently Director for the Program in Health Disparities Research and Associate Professor of Family Medicine at UMMS, where he leads an interdisciplinary team of scientists and trainees. He has a decade-long program of research on minority health and interventions targeting health disparities and has mentored minority students and faculty in this domain. The Co-Director, as Associate Professor in the School of Public Health, is Co-Chair of the School's Health Disparities Work Group. The goals of this Group include creating long-lasting partnerships with SPH faculty and the community, strengthen collaborations, and ensure health disparities is integrated into the curriculum. She has conducted a number of CBPR projects over the years and has mentored 1 P60 MD003422-01 16 ZMD1 PA (13) AHLUWALIA, J Concerns: There does not appear to be a formal process for developing/supervising student's projects. How will adequate mentorship/oversight of students by mentors be ensured? Is there a process in place for review/approval of the project itself?
Pre-doctoral program: 10 weeks/one summer, for students in health professional schools. Partnering with OCR summer fellowship program/UMN, which has trained 30 scholars/3 years. Adding 4 students a year from 3 HBCUs. How will they ensure a meaningful research experience in such a short time period?

Concerns:
The three letters of support from Howard (Dentistry, Medicine, and Pharmacy) are not on Howard university letterhead and are unsigned. The wording of all the letters is extremely similar, suggesting they have been written by the investigators, not the partners.
Concerns which apply to both programs: Neither of the Project PIs (Dr. Thomas, Dr. Israni) are listed as one of the core faculty members who will be available as mentors (p 344).

Cultural competency training for medical students:
The investigators propose that they will participate in an overall redesign of the medical student curriculum which is planned for 2010 to ensure cultural competency is woven throughout the medical education program. The application is vague about how this will be done, and by whom. It sounds as if planning for this new curriculum is already well underway, and it does not appear that the core directors have been part of the curriculum planning that has occurred up to this point. It is unknown whether the investigators in this core were part of the MED 2010 "Disparities in Health Working group" in Appendix D.
Investigator: Dr. Vickers (director) and Dr Ahluwalia (co-director) -2.4 months combined effort. They appear experienced and qualified as mentors. Also 1.8 mos administrator time.

Budget Recommendations: As requested
Administrative Comments: The three letters of support from Howard (Dentistry, Medicine, and Pharmacy) are not on Howard university letterhead and are unsigned. The wording of all the letters is extremely similar, suggesting they have been written by the investigators, not the partners.

CRITIQUE 2 OF THE RESEARCH/TRAINING AND EDUCATION CORE
Significance: Minorities are underrepresented in clinical medicine, clinical research, and education. Yet they are needed to create a culturally sensitive environment and provide role models for future generations. The Core's focus is to increase their numbers as clinicians, researchers, educators, and thus role models.
Approach: This core will 1) expand the partnership with the Minnesota Future Doctors Program (which enrolls 25 students annually) to select 4 talented students to engage in pre-MD/PhD research training, 2) Expand the office of Clinical Research Summer Pre-Doctoral Fellowship Program in Clinical and Translational Research to include talented health profession students from Howard University, Meharry Medical College, and Morehouse School of Medicine for summer pre-doctoral health disparities training, 3) Develop a cultural competency curriculum for medical students, students, faculty, and staff at the University of Minnesota, and 4) provide grant writing experience.
For the research training programs (undergraduate and health-related graduate students) there is cultural competence training (detail about the scope of this training was provided), a core curriculum, career development seminar series, and mentored research project. Detail about selecting mentors, guiding students, and evaluating their performance is provided. Routine evaluation of students and the 1 P60 MD003422-01 17 ZMD1 PA (13) AHLUWALIA, J research training program will be conducted. Excellent detail about the availability and selection of trainees was provided.
Investigator: The Director of this Core is the Jay Phillips Professor and Chair, Dept of Surgery, Associate Director of Translational Research, and a senior scientist at the Masonic Cancer Center. He was a founding member of the National Center on Minority Health and Health Disparities. The Co-Director is the PI for the Center. Both are very well qualified. The Program Manager has relevant experience.

Budget recommendations:
The budget appears to be commensurate with the proposed activities. (The amount for student travel to the Midwest conference seems excessive, but may foster attendance). Perhaps should be decreased.

CRITIQUE 3 OF THE RESEARCH/TRAINING AND EDUCATION CORE
Significance: Research training and education targeting minority investigators and trainees is critical to the success of health disparities research program. The CeHDRET research and education training core will an important role towards this objective.

Approach:
The core lists four specific aims. Several innovative training programs are proposed. The core reaches out Howard University, Meharry Medical College and the Morehouse School of Medicine. The core functions are well integrated into the CeHDRET.

Investigator:
The Principal Investigator -Selwyn M Vickers, MD, Jay Philips Professor and Chair, Department of Surgery is well qualified to lead this core. She was the PI of the University of Alabama NCMHD P60 grant before joining the University of Minnesota in 2006. Co-Investigators are well qualified.

Budget Recommendations:
The budget is appropriate to the proposed task.

CRITIQUE 4 OF THE RESEARCH/TRAINING AND EDUCATION CORE
Significance: This core will help in reducing health disparities and improving minority health by creating adequate number of investigators, health care providers, role models, and educators. The deficiency in the number of these leaders compounds the problem of persistent health disparities. Thus the overall goal of the Research Training and Education Core will be to cultivate, train, and grow the pool of minority academic investigators. These goals will be developed in the context of the comprehensive goal of the Center for Health Disparities Research, Engagement, and Training. Critical to addressing these problems will be intramural and extramural partnerships. This will build on existing programs within the University of Minnesota Medical School and Academic Health Center and will include partnerships with the traditional historically black medical institutions, specifically Howard University, Meharry Medical College, and Morehouse School of Medicine.

Approach:
The proposed core will benefit from the unique features of the partnering institutions and environment. The approach is acceptable and sound. The Research Training and Education Core will: As Director of this Core, Dr. Vickers will oversee the activities and personnel in this application, represent the Core during recruitment events, and conduct evaluations of all the students.

Environment:
The environment is excellent. The UM has a long-time, excellent reputation with minority communities of African Americans.

Training in Responsible Conduct for Research: Appropriate
Budget: Appropriate

1E. RESEARCH CORE (SCORE DESCIPTOR: OUTSTANDING) CORE LEADER (S): EVERSON-ROSE, SUSAN A DESCRIPTION: (As provided by applicant)
The Research Core for the proposed Center for Health Disparities Research, Engagement, and Teaching (CeHDRET) has two primary objectives. Our first objective is to promote research focused on health disparities and minority health at the University of Minnesota and with our Minneapolis and St. Paul metro area partners. The second objective is to provide an integrative "home base" for this research. Our goals are to improve the health of minority groups, and, ultimately, to eliminate health disparities across racial/ethnic groups. The Research Core has four Specific Aims. Aim 1 is to oversee the two primary research projects proposed for our Center. Project 1 is an innovative intervention study utilizing Community Health Workers and biomarker feedback to reduce African American children's exposure to secondhand tobacco smoke in the home and to encourage home smoking restrictions. Project 2 will use available national Medicare data to address disparities related to race/ethnicity and access to quality care in the management of and morbidity and mortality outcomes related to chronic kidney disease, an important, though often under-recognized public health problem disproportionately affecting African Americans. Aim 2 is to facilitate the development of innovative new research projects for external funding that address minority health concerns and health disparities. Aim 3 is to develop a collaborative and integrative approach for health disparities and minority health research. Aim 4 is to disseminate research findings to the academic community, community groups, health care providers and policy makers. We will achieve these aims by providing research infrastructure support; offering monthly "work in progress" research seminars to share work at various stages and facilitate exchange of ideas; establishing a Research Review Committee that provides a scientific "mock review" to maximize success of grant applications; and sponsor an annual "Accelerating the Future" research symposium highlighting 1 P60 MD003422-01

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ZMD1 PA (13) AHLUWALIA, J research of our investigators and trainees, featuring a keynote national speaker, and giving mentor, community leadership, and investigator awards. By integrating resources, interests, and opportunities related to health disparities and minority health, we will build research capacity and develop cutting edge research projects and programs.

CRITIQUE 1 OF THE RESEARCH CORE
Approach: The two primary projects do not appear to be thematically connected at all. The activities of the research core are well-described and specific, and laid-out in aims (p220). Infrastructure support is described. Particularly impressive are their plans to • encourage collaboration of research across the University (through annual research symposium, quarterly luncheon series); • to establish a research review committee which will offer mock reviews, advise new investigators • to foster new research projects via a University-funded pilot grant program. Up to 4 awards, $50,000 each, per year beginning year 2… with a system of formal review.
The process for selection of the two primary projects is well-described: an internal RFA soliciting a onepage proposal. 10 applications (8 listed in table 1?) were reviewed by a committee. Oversight of projects well-described, and will occur via biannual progress reports, annual meeting with executive committee. to oversee 2 independent research projects, 2) facilitate the development of new research to address this domain of minority health and health disparities, 3) develop and nurture collaborative, integrative, and translational research models in this domain, and 4) disseminate research findings broadly to scientists and the community. A broad solicitation across the academy for potential applicants was conducted, and two projects have been selected that addresses gaps among discovery, development, and delivery of health-related factors. One project focuses on improving minority health through smoking cessation and the other focuses on health disparities in chronic kidney patients.
For Aim 2 the Core is developing a Research Review Committee to provide feedback on grant applications prior to submission (it is composed of the Core Directors and Co-Directors, and 3-5 selected ad hoc reviewers from the University), to ensure the proposals are culturally sensitive, to have access to the resources at UM Centers (e.g., Health Survey Research and Biostatistics, Design, and Analysis Centers), and oversee the HD Pilot Research Grants Initiative (funded by the UMMS).
For Aim 3 the Core is sponsoring Accelerating the Future -a day-long University wide Research Symposium for investigators, policy makers, clinicians, and community partners, coordinating monthly trans-disciplinary research seminars, hosting a quarterly, 'building bridges' luncheon series to foster collaborations across the university (laudable and truly aiming to be trans-disciplinary), and coordinate the Community Dialogue Series research meetings quarterly. This Core will fund the Accelerating the Future Symposium Speaker Honorarium (for the keynote) and an External Grant Reviewer Honorarium (the Core's Research Review Committee will hold a mock NIH-like grant review, with those receiving scores of excellent given the possibility of an external review by a consultant).

Investigator: The Director of this Core is the Associate Director for the Program in Health Disparities
Research. She has appropriate research and administrative experience to oversee this Core. The Co-Director is Professor of Epidemiology and Community Health and Professor of Pediatrics. She has served as Associate Dean for student and academic affairs in the School of Public Health and is presently the Director of the National Program Office of the Robert Wood Johnson Foundation-funded Healthy Eating Research Program. The Program Manager has extensive experience with University and community initiatives, and is PM for another Core***.

Environment:
The physical resources, leadership, and university and community partnerships are excellent to foster the aims of this Core.

Targeted Recruitment for clinical trials: Acceptable
Vertebrate Animals: NA Animal Care and Use: NA Budget Recommendations: The budget appears to be commensurate with the proposed activities.

CRITIQUE 3 OF THE RESEARCH CORE
Significance: The CeHDRET research core will harmonize the investigative activities of the Center. This is an essential task in helping the Center to achieve its goals. 1 P60 MD003422-01 21 ZMD1 PA (13) AHLUWALIA, J Approach: Two objectives are listed for the Research Core. Several functions are outlined. The core will play important roles in the two specific research projects as it has already done in the process of selecting the projects prior to submission of the grant proposal.
Investigators: Dr. Everson-Rose is well qualified to direct the Research Core. The co-Investigators are well qualified.

Environment:
The environment at the University of Minnesota is outstanding in every respect necessary to accomplish the missions of the CeHDRET Budget Recommendations: The budget is appropriate for the proposed tasks.

CRITIQUE 4 OF THE RESEARCH CORE
Approach: This Research Core aims to promote research focused on health disparities and minority health at the University of Minnesota and to provide an integrative "home base" for research. The Research Core will oversee two primary research projects: the first intervention study utilizing Community Health Workers and biomarker feedback to reduce African American children's exposure to secondhand tobacco smoke in the home and to encourage home smoking restrictions. The second project will use available national Medicare data to address disparities related to race/ethnicity and access to quality care in the management of and morbidity and mortality outcomes related to chronic kidney disease, an important, though often under-recognized public health problem disproportionately affecting African Americans. The core will also facilitate the development of innovative new research projects for external funding that address minority health concerns and health disparities. It will develop a collaborative and integrative approach for health disparities and minority health research and disseminate research findings. Research at the University of Minnesota Medical School. Dr. Everson-Rose is a social epidemiologist and psychophysiologist who has considerable expertise and has published widely on the role of stress, psychosocial factors and socioeconomic factors in the development and progression of cardiovascular diseases, stroke and diabetes. She presently is funded by NHLBI to examine how individual and neighborhood level indicators of psychosocial stress contribute to stroke risk in an elderly population of African-Americans and Whites residing in Chicago and whether psychosocial vulnerability contributes to racial disparities in stroke. The Research Core Co-Director will be Mary Story, Ph.D., Professor in the School of Public Health and the Medical School's Department of Pediatrics with extensive experience in research and administration. Dr. Story served as Associate Dean for student and academic affairs in the School of Public Health until 2005, at which time she became Director of the National Program Office of the Robert Wood Johnson Foundation-funded Healthy Eating Research program. She currently is PI on Bright Start (R01 HL078846), a NIH-funded school and family-based obesity prevention study on the Pine Ridge (American Indian) reservation with kindergarten and first grade children. She has authored 280 scientific journal articles and been the PI on more than $15million in NIH funding, and the Co-Pi and Co-l on more than $20 million in NIH funding. Dr. Story has received several awards for her community-based work and research; in 2007 she was inducted into the University of Minnesota Academic Health Center (AHC) Academy for Excellence in Health Research, the high recognition of excellence in AHC faculty research.

Environment:
The environment is well suited for the project. The application details several plans for resource allocation, coordination and utilization. Strong letters of support are included. Exposure to environmental tobacco smoke (ETS) early in life increases the risk of sudden infant death syndrome, asthma, and respiratory infections contributing to more than 5,000 premature deaths among children in the US each year. African American children suffer disproportionately from the consequences of ETS exposure with well documented higher rates of sudden infant death and asthma. While the roots for these disparities are complex (e.g., poverty, poor housing conditions, environmental allergens), exposure to ETS is a prominent and quickly reversible cause of excess morbidity and mortality. We propose to address this deficit by providing culturally-sensitive biomarker feedback to the smoking parent/caregiver on their child's exposure to tobacco toxins. We will use a client centered motivationally enhanced counseling style to deliver the intervention. Further, delivery of this intervention by community health workers (CHWs) will further increase the salience of the proposed biomarker feedback intervention. With these points in mind, we propose a two-arm randomized clinical trail (N=180) to determine the efficacy of culturally sensitive biomarker feedback documenting a child's exposure to tobacco toxins (NNAL, nicotine, cotinine) to reduce home ETS exposure among African American children. Participants (i.e., the smoking parent or caregiver) will be randomized to receive one of two treatments: Tx1: General Home Safety Intervention -Contact Control Group (Lead Biomarker Feedback) Tx2: Home ETS Reduction Intervention -Treatment Group (Tobacco-Specific Biomarker Feedback) We hypothesize that tobacco-specific biomarker feedback will result in decreased home ETS (air nicotine levels) through increased parental smoking cessation and/or adoption of complete home smoking bans. This study will identify an innovative and effective strategy for reducing ETS exposure among African American children. The proposed delivery of culturally sensitive biomarker feedback can 1 P60 MD003422-01 23 ZMD1 PA (13) AHLUWALIA, J serve as a template for future efforts to bring the promise of personalized medicine to underserved populations.

CRITIQUE 1 OF THE RESEARCH PROJECT 1
Significance: Exposure to environmental tobacco smoke (ETS) increases the risk of many health risks for children, with African American children having a much greater burden than other groups. This project aims to provide child biomarker feedback to smoking adult parents/caregivers.

Approach:
A 2-arm randomized trial is proposed (N=180) to determine the efficacy of culturally sensitive biomarker feedback to parents/caregivers about child's exposure to ETS. The control group receives Lead biomarker feedback, and the treatment group receives tobacco-specific biomarker feedback. The expectation is that exposure to ETS feedback will reduce in-home air nicotine levels (primary outcome) and biomarkers in children (urinary cotinine; secondary outcome) over time because parent/caregivers have either reduced their smoking rates or have reduced smoking in the home (a mediator; and various psychological mediators are examined -e.g., optimistic bias, self-efficacy, social support). Community health workers will be trained to deliver the multi-session, home-based interventions (1 for smoking cessation, 1 for lead) using motivational counseling, this feedback will happen only once during week 2. There are clear inclusion/exclusion criteria.
The biggest concern with this intervention is that there are numerous approaches to motivate smoking cessation in smokers. Use of a standard of care in smoking cessation, rather than a lead-based comparison, would be a stronger test for hypotheses? The proposed intervention, while controlling for time and attention, is a very weak test for this intervention, which is based in part on motivational interviewing. A stronger test for the intervention would do much more for bringing 'science' to the 'community.' The use of the 7-day air badges as a primary outcome is somewhat worrisome because there is no way to ensure they were utilized the entire time.
Innovation: ETS biomarker feedback may be an effective strategy to reduce AA parental/caregiver tobacco use in the home. There is a paucity of research in this population that has a larger ETS burden and attention to constructs important for behavior change according to self-determination theory (i.e., autonomy, competence, and relatedness) have not been tried and should increase success.
Give control group no biomarker feedback and no motivational counseling.

Investigators:
The PI and Co-Investigators have a track record of research and funding in tobacco cessation research, and with culturally relevant experience. There are also Co-Investigators with biomarker collection, analysis, and feedback experience. Two community health workers will be hired from the community and trained in delivering the intervention. Two external consultants, one with expertise in smoking cessation and interventions, and one with expertise in the effects of airborne materials on health, will be utilized. Two internal consultants (no funds requested) are also delineated.

Environment:
The resources to conduct this research are very good. The community partnership and subcontract for ensuring a good response rate and for obtaining community health workers is very good.

Additional Review Criteria:
Human Subjects: A; DSMP in place, Certificate of Confidentiality will be sought What precautions will be made to ensure children will not be coerced into participating from their parent/caregiver, or that children will not be punished by caregiver for implicating him/her in 'bad' behavior? To help ensure adequate response rates for outcome assessments a subcontract with a community health center is in place. Two Community Health workers will be hired to carry out all in-home intervention activities and participate in weekly research meetings.

CRITIQUE 2 OF THE RESEARCH PROJECT 1
Significance: This project addresses a critical need to eliminate child exposure to environmental tobacco smoke (ETS) in African American homes. African American children have higher levels of cotinine-verified ETS exposure than non-Hispanic whites and Mexican Americans. The central hypothesis is that enhancing the cultural relevance and messages alliance of a client-centered, motivational counseling intervention and providing feedback on tobacco-specific biomarker levels in children in the homes will lead to decreased ETS exposure in the children, adoption of home smoking restrictions, and more, accurate parental perceptions of health risks of smoking for their family. To test this hypothesis, the applicants propose a two-arm randomized, controlled trial investigating the efficacy of feedback on tobacco-specific biomarkers in children and a tailored; motivationally enhanced counseling approach to decrease home ETS exposure. The biomarker feedback and counseling will be delivered by African American Community Health Workers (CHWs) in home visits. The control arm of the trial will receive information about home safety in an equal number of home visits. Participants will be 180 African American smokers with at least one child in the home recruited from North Minneapolis and surrounding neighborhoods where the majority of African Americans in Minneapolis reside. Research staff will be housed in the Center's new space in the University's community-based building located in the Northside Minneapolis community (see description in Administrative Core). This project builds upon Dr. Thomas' prior and currently funded work developing novel smoking cessation interventions for minority populations, including use of partner support and biomarker feedback, and extends this program of research to maximizing the cultural relevance of the intervention. This study has the potential to contribute to the field of evidence-based medicine. It may also help in reducing or eliminating health disparity among African American.
Approach: The conceptual, design, methods, and analyses adequately developed, well integrated to the aims of the project. The objective in the proposed application is to test whether the delivery of biomarker feedback documenting a child's exposure to environmental tobacco smoke will increase smoker quit rates and/or, increase the adoption of home smoking bans, ultimately decreasing home ETS exposure. They will train community health workers to use a motivationally enhanced counseling strategy to deliver the biomarker feedback intervention to increase message salience and enhance motivation. The proposed delivery of culturally sensitive biomarker feedback can serve as a template for future efforts to bring the promise of personalized medicine to underserved populations. However, the approach is not very innovative.
Investigators: This team is well-qualified to carry out the proposed study. This is a multidisciplinary clinical team that comprises a general internist with expertise in health disparities and diabetes Janet L. smokers. These projects include behavioral and pharmacologic interventions, qualitative analyses, and survey development. For this project, Dr. Thomas will provide overall study direction and will work closely with the team from North point Health and Wellness Center, Inc. (subcontract) to supervise the implementation of the CHW delivered motivationally-enhanced delivery of the biomarker feedback and home smoking intervention. Dr. Thomas will be responsible for the development of the assessment surveys and will work closely with Drs. An, Hennrikus and Borrelli in developing the counseling intervention. She will train the study research staffon participant enrollment, informed consent, assessment completion, and will work with Dr. Ramirez-Barrett (North point Health and Wellness Center, Inc., Director) to monitor the fidelity of the CHW-delivered counseling intervention. She will work with Drs. Hennrikus and Borrelli to develop the counselor training materials for this project and will oversee the counselor training sessions. With the Project Coordinator, she will run weekly investigator meetings (with Dr. Ramirez-Barrett joining by phone). Dr. An is a seasoned tobacco researcher, having received two smoking intervention R01 grants from NHLBI to investigate web based access to NRT to facilitate smoking cessation and another designed to provide college students with behavioral strategies to quit via an internet site. Deborah Hennrikus, Ph.D. -Associate Professor in the School of Public Health, Division of Epidemiology and Community Health, will serve as Co-Investigator of Project 1. Dr. Hennrikus is a behavioral scientist and an Associate Professor in the Division of Epidemiology and Community Health, School of Public Health, University of Minnesota. She has extensive experience in community-based research projects to assess interventions to decrease to exposure to environmental tobacco smoke.

Environment:
The investigative team has access to patients in these clinics and a letter of support signed by both the Executive Director and Medical Director is strong.

Inclusion of Children Plan: Appropriate
Budget: Reasonable.

CRITIQUE 3 OF THE RESEARCH PROJECT 1
Significance: Environmental Tobacco Smoke (ETS) is an important cause of morbidity and mortality with disproportionate impact on minority populations. Proven interventions that could alleviate this exposure particularly in children are needed Approach: Client centered motivationally enhanced counseling will be delivered to the smoking parent or caregiver in a randomized fashion to two treatment groups: Lead Biomarker Feedback and Tobacco-Specific Biomarker Feedback. Two hypotheses will be tested on the outcomes: air nicotine level (primary outcome) and smoking cessation or complete smoking bans.

Innovation:
The experimental design is innovative Personnel budget effort appear to be excessive in several categories • The budgeted effort for the PI is excessive and should be reduced. 20% is suggested • The budgeted effort for each of the three co-investigators effort is excessive. 5% effort is suggested for Drs. Ahluwalia, An, Hennrik us and Luo • The budgeted effort for Database Manager is excessive. 10% effort is suggested

CRITIQUE 4 OF THE RESEARCH PROJECT 1
Significance: ETS exposure in children is an important, modifiable public health concern -associated with asthma, SIDS, and possibly long-term risk for malignancy and CVD. ETS exposure is higher among AA children as compared with white children. But is there evidence that childhood diseases resulting from ETS are disparity conditions?
Aims 1 and 2 are closely related, and really should be considered sub-aims: two different ways of measuring the same thing. This home-based motivational-interviewing intervention seems quite laborintensive. If successful, will it be practical to implement ? Who will pay for it?
Approach: Staged phases including focus group and pilot phase prior to RCT are impressive and seem to be well-designed and likely to succeed. The intervention will be developed in the initial phases with community feedback.
How will urine samples be collected on children that are not yet toilet trained?
Tobacco use is higher in African-American men as compared with African-American women; yet it is likely that most of the adults recruited into the study will be mothers rather than fathers. This is a potential weakness. 1 P60 MD003422-01 27 ZMD1 PA (13) AHLUWALIA, J Innovation: Use of focus groups to pilot and refine the cultural relevance of the intervention is impressive and innovative. There is a thorough and systematic plan for analysis of focus group data.
The plan to assess psychological motivators for change (exploratory aim) is innovative and may be interesting.
Investigators: Application clearly demonstrates expertise and experience in conducting studies in smoking cessation using behavioral home-based interventions; also experienced in quantifying ETS exposure.

Environment: Adequate/supportive
Human Subjects: Though all participants will receive general information on smoking cessation, it does not appear that the control group will receive even basic educational information on the harmful effects of ETS exposure in their children. This seems negligent. HS protection for the kids is not clearly mentioned.

Risks and Protections: Acceptable
Inclusion of Women: Acceptable. They project 50/50 men and women; but more women are likely expected than men… Table 6 is not likely to accurately reflect the gender distribution.

1F-2 RESEARCHG PROJECT 2 -Health Disparities in Treatment, Cardiovascular Morbidity and Mortality of Chronic Kidney patients in the US (PRIORITY SCORE 269)
PROJECT LEADER: ISRANI, AJAY K DESCRIPTION (as provided by applicant): Chronic kidney disease (CKD) affects an estimated 26 million Americans (or 13% of the adult U.S. population), and it is well known that CKD is an independent risk factor for atherosclerotic heart disease (ASHD) and mortality. These complications of CKD are more common in African Americans than Whites. These complications can be prevented by timely referral to a nephrologist and quality CKD care in order to prevent ASHD. Our preliminary studies show regional variations in lack of appropriate physician follow-up. Disparities in delivery of quality CKD care and their impact on the worse outcomes seen in African Americans have not been adequately described for Medicare beneficiaries with CKD. Therefore, it is important to determine whether physicians are adhering to existing evidence based guidelines which call for recognizing CKD as a potent risk factor for cardiovascular disease and aggressively monitoring serum creatinine, lipids, calcium-phosphorus, hemoglobin A1c (in diabetics) and parathyroid hormone. Other aspects of quality CKD care for African Americans entail providing preventive healthcare such as influenza vaccinations annually and timely referral to a nephrologist. The specific aims are: 1) To determine if African Americans are less likely than Whites to receive quality CKD care. (2) To determine if quality of CKD care independently explains the worse outcomes in African American Medicare patients. Outcome measures .include patient death and atherosclerotic heart disease 1 P60 MD003422-01 30 ZMD1 PA (13) AHLUWALIA, J 3. "Definition" of CKD: (p. 309-310). Choice of specific ICD-9 codes for inclusion is far too broad, and will include large numbers of subjects without CKD: 9 of the 38 ICD-9 codes used for inclusion are not characterized by CKD, and several others are questionable. Since only one inpatient claim is required for inclusion, a large number of patients without CKD will be included. It is as if they took as broad a swathe as possible, including any diagnosis which has the word "kidney" or "renal" in it to maximize their sample size. This definition does not match up with the quality of care outcome measures chosen (see below). 4. "At least one inpatient OR at least two outpatient claim codes" (p. 309-310); "at least one inpatient AND at least two outpatient claim codes" (p. 314). This is a critical distinction. Both have flaws (the latter: patients will only be included if they are hospitalized during the study period). 5. "Our CKD claims algorithm will be validated and fine-tuned as part of this proposal" -This should be a major aim, not just a two-paragraph side note. The authors need to describe their validation procedure in more detail. a. How do they define CKD (ie, what is their gold standard)? -NKF stages themselves are designed for coding/billing purposes and are not rigorous enough to stand alone as research definitions. b. They propose to validate their claims strategy in 1170 subjects with CKD, ie, sensitivity; will they also assess false positives/specificity, which I see as a more important weakness? i.e, will they determine how often patients without CKD are inappropriately characterized as having CKD? c. What is their goal/standard for specificity and sensitivity? Will specific diagnoses be discarded if they do not meet certain sense/spec cut-offs? What is the procedure for making this determination? d. Will this assessment be completed prior to, or contemporaneously with, completion of the proposed study? Timeline on p. 322 suggests it will be completed (and Aim 1 analysis will begin) in the second half of the first year. This does not seem realistic, and does not allow for time to validate/modify/revalidate their algorithm in a systematic way. 6. Investigators cite prior work using Medicare claims database to assess disparity outcomes; but this prior work (patterns of care for kidney transplant recipients; access to transplant) studies populations who have de facto automatic medicare eligibility; AND the diagnosis codes for these conditions are much clearer and more likely to be coded properly. Neither of these important conditions holds for the current study.

Outcome Measures
Their definition of "quality CKD care" is questionable given their chosen outcomes. Is yearly influenza vaccination likely to be associated with excess CVD and mortality outcomes? Table 4 (p. 304) -They took K-DOQI guideline recommendations for CKD stage 3-4 and apply them as standard of care in a population which appears to include CKD 1-2 -and given the flaws in their design, will also include many patients without any CKD at all. Specifically, Ca/P/PTH once a year are recommended only for CKD stage 3+; nephrologist visit is explicitly recommended only for CKD stage 4+; more than yearly Cr is recommended only for CKD stage 3+.
In addition, they omit several measures that are considered to be important standards of care (some of which can be assessed using Medicare claims, many of which cannot); ie, measurement of albuminuria in diabetics; measurement and control of blood pressure; screening for anemia; timely dialysis access placement.
Late referral to a nephrologist among African Americans appears to already be well-established.
Worsening renal function, or at least progression to ESRD (which is easy to measure in their dataset), should be one of their outcomes. Mortality and ASHD in YEAR 3 ONLY will be counted. Patients enrolled in year 1 who die in year 2 will be excluded; mortality and ASHD events in year 4+ will not be measured. This is severely limiting. At a minimum, mortality and ASHD events in year 2+ for which data is available should be included as endpoints.
For Aim 3 (looking at relationship between density and ratio of providers and disparities) -they propose to examine the association between provider density and disparities in preventative measures. They should also look directly for an association between provider density and disparities in outcomes (ASHD, mortality). For example, patients may be less likely to see a nephrologist yearly in an area with lower density of specialists; but this may or may not translate into worse outcomes.

Innovation:
The authors have already shown in their preliminary data that, in the medicare claims dataset from mid-1990s, AAs are less likely to have lipid testing, influenza vaccination, PCP visit, and HbA1c testing (for diabetics). It seems they are measuring many of the same endpoints, just in a different subgroup (those with CKD).

Investigators:
Dr. Israni's degree is given as Ph.D. on the face page (p 292) but as M.D., M.S. under personnel/budget justification. He is a nephrologist at Hennepin county Medical Center. He is a K23 awardee and project leader on a U19. He is experienced in studying health disparities using Medicare claims data (post-transplant care). Dr. Kasiske, his K23 mentor, is Co-investigator. He is also experienced user of Medicare claims dataset to study transplant access disparities.
Environment: Appears to be satisfactory.

OVERALL EVALUATION:
Although disparities in CKD care and progression are an important cause of increased morbidity and mortality in African Americans in the United States, there are several critical flaws in the design of this proposal which will render its conclusions close to meaningless. Because of this, enthusiasm for this proposal is quite low and this reviewer rated it as barely acceptable. Significance: This project addresses racial/ethnic disparities and access to quality care that impact the management and ultimately the morbidity and mortality associated with chronic kidney disease (CKD). Minorities, especially African Americans, experience a disproportionate burden of CKD, including faster progression to ESRD requiring dialysis or kidney transplantation. CKD contributes to 1 P60 MD003422-01 32 ZMD1 PA (13) AHLUWALIA, J significant impairments in quality of life and is a potent risk factor for cardiovascular disease. Evidence suggests minorities are less likely than Whites to be aware of their CKD, raising the possibility that disparities in CKD outcomes may result from disparities in management and treatment of CKD risk factors in minority groups. The central hypothesis is that the excess morbidity and mortality outcomes related to CKD observed in African Americans result from disparities inequality of CKD care. A secondary hypothesis is that disparities in quality of CKD care vary within regions of the US. Dr. Israni and colleagues will use available Medicare Claim s data to determine quality of CKD care received by African American patients, compared with White patients, and whether poorer quality care contributes to excess morbidity and mortality related to CKD that has been observed in African Americans. These investigators also will determine which parts of the US have greater disparity in quality of CKD care and whether density of providers (primary care physicians and nephrologists) or ratio of primary care physicians to nephrologists contribute to disparities in CKD care. Using available national administrative data enables Dr. Israni and colleagues to test their hypotheses in a highly efficient, cost-effective manner. This project builds upon Dr. Israni's prior work, funded by the Robert Wood Johnson Foundation, examining disparities in minority access to nephrologists following kidney transplantation and addresses an important disparity in CKD outcomes.